State of the Art: Acute Encephalitis

Clin Infect Dis. 2023 Sep 11;77(5):e14-e33. doi: 10.1093/cid/ciad306.


Encephalitis is a devastating neurologic disease often complicated by prolonged neurologic deficits. Best practices for the management of adult patients include universal testing for a core group of etiologies, including herpes simplex virus (HSV)-1, varicella zoster virus (VZV), enteroviruses, West Nile virus, and anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody encephalitis. Empiric acyclovir therapy should be started at presentation and in selected cases continued until a second HSV-1 polymerase chain reaction test is negative. Acyclovir dose can be increased for VZV encephalitis. Supportive care is necessary for other viral etiologies. Patients in whom no cause for encephalitis is identified represent a particular challenge. Management includes repeat brain magnetic resonance imaging, imaging for occult malignancy, and empiric immunomodulatory treatment for autoimmune conditions. Next-generation sequencing (NGS) or brain biopsy should be considered. The rapid pace of discovery regarding autoimmune encephalitis and the development of advanced molecular tests such as NGS have improved diagnosis and outcomes. Research priorities include development of novel therapeutics.

Keywords: HSV-1 encephalitis; West Nile virus encephalitis; anti-NMDAR antibody encephalitis; encephalitis review; next-generation sequencing.

MeSH terms

  • Acyclovir / therapeutic use
  • Adult
  • Brain / diagnostic imaging
  • Encephalitis* / diagnosis
  • Encephalitis* / drug therapy
  • Encephalitis, Herpes Simplex* / diagnosis
  • Encephalitis, Herpes Simplex* / drug therapy
  • Herpesvirus 1, Human*
  • Herpesvirus 3, Human
  • Humans
  • Nervous System Diseases*


  • Acyclovir